Ist ein Hämatokrit von 80% mit dem Leben vereinbar? Die Antwort lautet: NO

Is a hematocrit level of 80% supportable? The answer is: NO. Nitric oxide (NO) induces vasodilatatory, antiaggregatory, and antiproliferative effects Nitric oxide (NO) induces vasodilatatory, antiaggregatory, and antiproliferative effects in vitro. To delineate potential beneficial effects of NO in preventing vascular disease in vivo, we generated transgenic mice overexpressing human erythropoietin. These animals induce polyglobulia known to be associated with a high incidence of vascular disease. Despite hematocrit levels of 80%, adult transgenic mice did develop neither hypertension nor thromboembolism. Endothelial NO synthase (eNOS) levels, NO-mediated endothelium-dependent relaxation and circulating and vascular tissue NO levels were markedly increased. Administration of the NO synthase inhibitor L-NAME led to vasoconstriction of peripheral resistance vessels, hypertension and death of transgenic mice, while wildtype siblings developed hypertension, but did not show increased mortality. L-NAME-treated polyglobulic mice revealed acute left ventricular dilatation and vascular engorgement associated with pulmonary congestion and hemorrhage. In conclusion, we here unequivocally demonstrate that endothelial NO maintains normotension, prevents cardiovascular dysfunction and critically determines in vivo survival under conditions of increased hematocrit.. To delineate potential beneficial effects of NO in preventing vascular disease in vivo, we generated transgenic mice overexpressing human erythropoietin. These animals induce polyglobulia known to be associated with a high incidence of vascular disease. Despite hematocrit levels of 80%, adult transgenic mice did develop neither hypertension nor thromboembolism. Endothelial NO synthase (eNOS) levels, NO-mediated endothelium-dependent relaxation and circulating and vascular tissue NO levels were markedly increased. Administration of the NO synthase inhibitor L-NAME led to vasoconstriction of peripheral resistance vessels, hypertension and death of transgenic mice, while wildtype siblings developed hypertension, but did not show increased mortality. L-NAME-treated polyglobulic mice revealed acute left ventricular dilatation and vascular engorgement associated with pulmonary congestion and hemorrhage. In conclusion, we here unequivocally demonstrate that endothelial NO maintains normotension, prevents cardiovascular dysfunction and critically determines in vivo survival under conditions of increased hematocrit.